rs3752752

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022124.6(CDH23):c.2316T>C(p.Asn772Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,611,520 control chromosomes in the GnomAD database, including 375,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30289 hom., cov: 34)

Exomes 𝑓: 0.68 ( 344852 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -1.08

Publications

34 publications found

Variant links:

Genes affected

CDH23 (HGNC:13733): (cadherin related 23) This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described. [provided by RefSeq, May 2013]

CDH23 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 12
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Usher syndrome type 1
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 1D
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CDH23 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 10-71695444-T-C is Benign according to our data. Variant chr10-71695444-T-C is described in ClinVar as Benign. ClinVar VariationId is 45893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CDH23	NM_022124.6 link	c.2316T>C	p.Asn772Asn	synonymous_variant	Exon 22 of 70	ENST00000224721.12	NP_071407.4
CDH23	NM_001171930.2 link	c.2316T>C	p.Asn772Asn	synonymous_variant	Exon 22 of 32		NP_001165401.1
CDH23	NM_001171931.2 link	c.2316T>C	p.Asn772Asn	synonymous_variant	Exon 22 of 26		NP_001165402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 link	c.2316T>C	p.Asn772Asn	synonymous_variant	Exon 22 of 70	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

95005

AN:

151954

Hom.:

30281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.528

Gnomad AMI

AF:

0.657

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.781

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.554

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.654

GnomAD2 exomes

AF:

0.628

AC:

156598

AN:

249186

AF XY:

0.641

show subpopulations

Gnomad AFR exome

AF:

0.521

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.765

Gnomad EAS exome

AF:

0.503

Gnomad FIN exome

AF:

0.558

Gnomad NFE exome

AF:

0.712

Gnomad OTH exome

AF:

0.656

GnomAD4 exome

AF:

0.683

AC:

997094

AN:

1459448

Hom.:

344852

Cov.:

AF XY:

0.684

AC XY:

496665

AN XY:

726120

show subpopulations

African (AFR)

AF:

0.512

AC:

17109

AN:

33436

American (AMR)

AF:

0.475

AC:

21249

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.771

AC:

20130

AN:

26108

East Asian (EAS)

AF:

0.483

AC:

19151

AN:

39686

South Asian (SAS)

AF:

0.634

AC:

54665

AN:

86214

European-Finnish (FIN)

AF:

0.566

AC:

30189

AN:

53366

Middle Eastern (MID)

AF:

0.702

AC:

4045

AN:

5766

European-Non Finnish (NFE)

AF:

0.712

AC:

790163

AN:

1109842

Other (OTH)

AF:

0.670

AC:

40393

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

15234

30467

45701

60934

76168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19606

39212

58818

78424

98030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.625

AC:

95044

AN:

152072

Hom.:

30289

Cov.:

AF XY:

0.617

AC XY:

45890

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.528

AC:

21896

AN:

41478

American (AMR)

AF:

0.564

AC:

8621

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.781

AC:

2711

AN:

3470

East Asian (EAS)

AF:

0.478

AC:

2463

AN:

5154

South Asian (SAS)

AF:

0.618

AC:

2979

AN:

4818

European-Finnish (FIN)

AF:

0.554

AC:

5860

AN:

10584

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.711

AC:

48348

AN:

67956

Other (OTH)

AF:

0.650

AC:

1371

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1801

3602

5404

7205

9006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.683

Hom.:

137860

Bravo

AF:

0.623

Asia WGS

AF:

0.523

AC:

1819

AN:

3478

EpiCase

AF:

0.727

EpiControl

AF:

0.731

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Caucasian frequency = 4989/6832 (ESP data) -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1D

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal recessive nonsyndromic hearing loss 12

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.16

(source)

DANN

Benign

0.45

PhyloP100

-1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over